Objective: To describe the positive rates of high-risk human papillomavirus (HR-HPV) DNA and serum-neutralizing antibody in cervical intraepithelial neoplasia (CIN) tissues of rural women in Xiangyuan County, Shanxi Province, and evaluate the association of HR-HPV DNA and neutralizing antibody positive status with the occurrence of CIN. Methods: In a cohort of 1 897 women aged 35-45 years established by the Shanxi Province Cervical Cancer Screening StudyⅠ, DNA typing (SPF10 PCR-DEIA-LiPA25) was performed by using tissue samples of women with positive HR-HPV test results [Hybrid CaptureⅡ(HC2)] or abnormal cytological or pathological results. Serum HR-HPV neutralizing antibody detection was conducted with multicolor pseudovirion-based neutralization assay. Cochran-Armitage trend test was used to analyze the changing trend of the positive rate of HR-HPV DNA and neutralizing antibody with the progression of CIN. Multivariate logistic regression models were used to evaluate the influence and multiplicative interaction of HR-HPV DNA and neutralizing antibody positive status on the occurrence of CIN. The relative excess risk (RERI), attributable proportion of interaction (AP), and the synergy index (SI) of the interaction were calculated to evaluate the additive interaction of HR-HPV DNA and neutralizing antibody on the occurrence of CIN. Results: The positive rate of any type of HR-HPV DNA (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) in 479 women who were HC2 positive or had abnormal cytological or pathological detection results was 37.16%. In normal, CIN1, CIN2, and CIN3+ groups, the HR-HPV DNA positive rates were 18.03%, 49.53%, 90.24% and 94.59%, respectively. The positive rate of any type of HR-HPV neutralizing antibody was 63.88%. In normal, CIN1, CIN2, and CIN3+ groups, the positive rates of HR-HPV neutralizing antibody were 63.95%, 57.94%, 70.73%, and 72.97%, respectively. The positive rate of any type of HR-HPV neutralizing antibody was 53.31% in 1 418 women who were HC2 negative and had normal cytopathology, and the most common types were HPV51 (27.36%) and HPV39 (24.96%). Multivariate logistic regression analysis showed that any type of HR-HPV DNA positive status (OR=9.15, 95%CI: 5.99-14.20, P<0.001) was the independent factor for the occurrence of CIN, HR-HPV neutralizing antibody positive status was not associated with the occurrence of CIN (OR=0.95, 95%CI: 0.61-1.48, P=0.815). The OR value of the multiplication of HR-HPV DNA and neutralizing antibody positive status of the occurrence of CIN was 1.63 (95%CI: 0.67-3.95), P=0.283. Quantitative analysis of interaction showed that RERI was 1.65 (95%CI:-3.56-6.86), SI was 1.28 (95%CI: 0.58-2.82), and AP was 0.19 (95%CI:-0.36-0.75). Conclusions: HR-HPV DNA positive status was a risk factor for the occurrence of CIN, but neutralizing antibody positive status was not associated with the occurrence of CIN. They had no significant multiplicative or additive interaction with the occurrence of CIN.
目的： 描述山西省襄垣县农村女性高危型人乳头瘤病毒（HR-HPV）DNA和血清中和抗体在宫颈上皮内瘤变（CIN）组织中的分布，并评估HR-HPV DNA和中和抗体阳性与发生CIN的关联。 方法： 在山西省襄垣县宫颈癌筛查方法研究Ⅰ建立的1 897名35~45岁女性队列中，对HR-HPV检测［第二代杂交捕获技术（HC2）］阳性或细胞学或组织病理异常女性的宫颈组织标本进行DNA分型（SPF10 PCR-DEIA-LiPA25），通过多色假病毒中和抗体试验检测女性血清中的HR-HPV中和抗体。采用Cochran-Armitage趋势检验分析HR-HPV DNA和中和抗体阳性率随着CIN严重程度的变化趋势，使用多因素logistic回归模型评估HR-HPV DNA和中和抗体阳性对发生CIN的影响及相乘交互作用。计算相对超额危险度（RERI）、交互作用归因比（AP）和交互作用指数（SI）评估HR-HPV DNA和中和抗体阳性对发生CIN的相加交互作用。 结果： 在479名HC2阳性或细胞学或组织病理异常的女性中，任一HR-HPV DNA（HPV16、18、31、33、35、39、45、51、52、56、58、59、68）阳性率为37.16%，在病理正常、CIN1级（CIN1）、2级（CIN2）、3级及以上（CIN3+）组织中分别为18.03%、49.53%、90.24%和94.59%。任一HR-HPV中和抗体阳性率为63.88%，在病理正常、CIN1、CIN2和CIN3+组织中分别为63.95%、57.94%、70.73%和72.97%。在1 418名HC2阴性且细胞、组织病理正常的女性中，任一HR-HPV中和抗体阳性率为53.31%，其中常见的型别为HPV51（27.36%）和HPV39（24.96%）。多因素logistic回归分析结果显示，任一HR-HPV DNA阳性是发生CIN的独立影响因素（OR=9.15，95%CI：5.99~14.20，P<0.001），任一HR-HPV中和抗体阳性与其无关（OR=0.95，95%CI：0.61~1.48，P=0.815）。HR-HPV DNA与中和抗体阳性的乘积项无统计学意义，两者对CIN发生风险的OR值为1.63（95%CI：0.67~3.95），P=0.283。相加交互作用定量分析结果显示，RERI=1.65（95%CI：-3.56~6.86），SI=1.28（95%CI：0.58~2.82），AP=0.19（95%CI：-0.36~0.75）。 结论： 任一HR-HPV DNA阳性是发生CIN的危险因素，但中和抗体阳性与发生CIN无关，两者对发生CIN无相乘或相加交互作用。.